Background: This study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leaks and assess their outcomes following endoscopic endonasal approach (EEA) for resection of skull base tumors. Methods: A retrospective review was conducted of patients who underwent EEA for resection of intradural pathology between October 2001 and October 2023. Data on demographics, approach type, reconstruction technique, tumor pathology, complications and outcomes were analyzed. Results: A total of 542 patients were included, with 80.1% undergoing surgery for sellar or suprasellar pathology. Lumbar drains were used in 14.9%, and dural sealants in 57.7%. Forty patients (7.3%) developed postoperative CSF leaks, with the highest rate in sellar or suprasellar lesions (5.9%). CSF leaks were associated with longer hospital stays (p < 0.001), higher 30-day readmission rates (p < 0.001), increased sepsis risk (p = 0.021), and higher rates of diabetes insipidus (p < 0.001). Lumbar drains increased the incidence of CSF leaks (p = 0.021), while nasoseptal flap reconstruction reduced leak rates (p = 0.0015). Higher BMI and intraoperative CSF leaks were also significant risk factors (p = 0.001) Conclusions: CSF leaks are associated with increased complications and extended hospital stays, highlighting the need for vigilant intraoperative monitoring and targeted strategies.

Background: Tuberous Sclerosis Complex (TSC) is a multisystemic neurocutaneous disorder in which hamartomas confer significant medical risks, including mortality, by disruption of local tissues. However, only recently have multiple studies assessed specific aetiologies of mortality in TSC. Methods: A literature review of all available studies examining mortality in TSC was conducted until December 15, 2024. Results: We identified 13 studies reporting 411 deaths from 6735 individuals with TSC. Crude mortality per 100 individuals ranged from 1.4-13.8 over average intervals of 11-45 years. Mortality risk ranged from 3.0-4.9 (mean 4.3) versus the general population. Mean life expectancy was 66.2 years compared to 81.8 in the general population. In seven studies that reported specific aetiologies of mortality, 6/7 (85%) had renal (commonly renal failure or angiomyolipoma hemorrhage) or brain disease (most frequently sudden unexpected death in epilepsy or brain tumours) as the most common cause of mortality. Intellectual delay conferred increased mortality risk. Lymphangioleiomyomatosis conferred significant risk of mortality in adult women and cardiac rhabdomyomas were the dominant cause of neonatal mortality. Conclusions: Mortality in TSC is elevated compared to the general population, with brain and renal disease most frequently culpable. Future studies should assess the impact of disease modifying therapies on mortality in TSC.

Background: Inuit children have been observed to have high rates of macrocephaly, which leads to burdensome travel for medical evaluation, often with no pathology identified. Given reports that WHO growth charts may not reflect all populations, we compared head circumference (HC) measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted HC data from a retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children, born between 2010-2013, and residing in Nunavut. We excluded children with preterm birth, documented neurologic/genetic disease, and most congenital anomalies. We compared HC values with the 2007 WHO charts. Results: We analyzed records of 1960 Inuit children (8866 data points). Most data were from ages 0-36 months. At all age points, the cohort had statistically significantly larger HC than WHO medians. At age 12 months, median HC were 1.3 cm and 1.5 cm larger for male and female Inuit children. Using WHO growth curves, macrocephaly was overdiagnosed and microcephaly underdiagnosed. Conclusions: Our results support the observation that Inuit children from Nunavut have larger HCs, and use of the WHO charts may lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population specific growth curves for Inuit children should be considered.

Background: Routine early postoperative CT (EPCT) in neurologically intact patients is unsupported but still common. Recent studies suggest 135 scans are needed to detect one clinically silent abnormality (Blumrich, 2021). This study assessed the rate and utility of EPCT, defined as a CT head scan within 24 hours of adult craniotomy. Methods: Retrospective review of adult craniotomy cases at the University of Alberta Hospital was conducted over a 10-month period. Data on EPCT rates, timing, adverse findings (complication or unfavourable outcome, e.g., bleeding, extensive pneumocephalus, edema, ischemia), as well as clinical data on neurologic deterioration (e.g., weakness, aphasia, visual impairment, decreased LOC), and repeat surgical interventions were extracted. Results: Of 405 patients (200 female, 54.6 ± 0.8 years, range: 19-89), 96.5% (391/405) underwent EPCT. Adverse EPCTs occurred in 9.2% (36/391), with neurologic deterioration in 7.7% (30/391) and repeat surgery in 2.8% (11/391). Adverse scans and neurologic deterioration were strongly correlated (X2=141.1, p=1.54e-32). Only 0.5% (2/405) of EPCT findings prompting surgery lacked prior neurologic deterioration. Conclusions: EPCT in the absence of neurologic deterioration has a low yield for surgical intervention and may be safely omitted.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.

Background: The use of Tenecteplase (TNK) in Extended Time Window (ETW) for Acute Ischemic Stroke (AIS) remains an ongoing debate. Methods: Systematic review of 3 Randomized controlled trials (RCTs)- TIMELESS, TRACE 3, CHABLIS-T II was conducted. Results: 1198 patients were enrolled: 603 received TNK, while 595 were controls. All 3 trials included patients with Internal Carotid and/ or Proximal Middle Cerebral Artery Occlusions; however, in TRACE 3, patients did not have access to endovascular thrombectomy. TIMELESS and CHABLIS-T II showed better recanalization in the TNK group but the median Modified Rankin Score was 3 at 90 days in both groups, demonstrating no benefit in clinical outcomes. Symptomatic Intracranial hemorrhage (sICH) was similar in the two groups. In TRACE 3, there was an improvement in functional outcomes at 90 days in the TNK group (33.0% vs. 24.2%), but the incidence of sICH was also higher (3.0% and 0.8%, respectively). Conclusions: Better recanalization rates are seen with TNK in ETW, but may not be associated with improved functional outcomes at 90 days compared to medical management. Incidence of sICH also remains largely favorable, except in TRACE 3, which showed a higher incidence in the TNK group. There remains a need for more RCTs in this population.

Background: Experimental and clinical evidence suggest that Parkinson’s disease (PD) manifests differently between females and males, yet women have been underrepresented in PD clinical research, leading to a limited understanding of the sex- and gender-specific aspects of the disease. Understanding the needs of women with PD (WwPD) is critical Methods: Patient-centered outcomes-based mixed methods study. Phase 1: Qualitative focus groups, patient-centered discussions, led by female interviewers. Phase 2: Nationwide survey via the Qualtrics platform, informed by focus group findings. We report the Phase 1 preliminary results Results: We conducted 5 focus groups with 22 cisgender women. Mean age 60.5 (range: 44 -81) and disease duration of 6.82 years. Two main themes emerged: (1) Mental Health: participants reported significant emotional distress, altered self-image, and impacts on family, social, and professional life. (2) Physical Health and Health care: While some were satisfied with care, those with young-onset PD experienced misdiagnosis, dismissal, and inadequate information. Sexual health, and the overlap between menopause and PD symptoms, were highlighted. Most participants emphasized the benefits of physical activity, nutrition, and social support. Conclusions: Findings highlight significant health challenges in women, underscoring the need for gender-specific care and tailored support to improve healthcare outcomes

Background: Postoperative visual deterioration following endoscopic endonasal surgery for pituitary adenoma is very rare yet significant morbidity. Visual deficit can arise from iatrogenic injury, compression or ischemic insults. The specific predictors of visual decline and their correlation with the effectiveness of various interventions remain poorly understood. Methods: We retrospectively reviewed data from790 patients who underwent endoscopic endonasal surgery for pituitary adenoma between 2014-2024. We included all the patients who had New Postoperative visual deterioration. Demographic, preoperative, intraoperative, postoperative data were collected and analyzed. Results: Nine patients (1.13%) experienced early postoperative visual deterioration. None of the patient has intraoperative report of direct injury to the optic apparatus, ischemic etiology was seen in five patients. Four patients underwent early reoperation to explore and decompress the optic apparatus. Vision was restored to baseline after reoperation in all 4 compressive cases. In the ischemic group (n=5), three patients improved with supplemental oxygen and hypervolemic-hypertensive therapy (p=0.03). Conclusions: Prognosis and outcome of Postoperative visual deterioration depends on the underlying cause and the effectiveness of intervention. Compressive etiology has a favorable prognosis when identified and managed with reoperation and decompression. Ischemic etiology potentially treatable with supplemental oxygen hypervolemic-hypertensive and high mean arterial pressure in more than half of cases.

Background: We summarize the efficacy and safety data for omaveloxolone in patients with Friedreich ataxia from the MOXIe clinical trial (NCT02255435, EudraCT2015-002762-23) and post hoc analyses. Methods: In MOXIe Part 2, patients aged 16-40 were randomized 1:1 to receive omaveloxolone 150 mg or placebo. The primary outcome was change in modified Friedreich Ataxia Rating Scale (mFARS) from baseline to Week 48—patients could roll over into an open-label extension (OLE). A post hoc propensity-matched analysis compared treated and untreated patients over 3 years. Results: Treatment with omaveloxolone significantly improved mFARS relative to placebo at Week 48, with a difference of -2.41 points for the full analysis set (n=82 [excluding severe pes cavus]; p=0.01) and -1.93 points for the all-randomized population (n=103 [including severe pes cavus]; p=0.03). Transient and reversible changes in aminotransferase levels were observed with omaveloxolone without other signs of liver injury. Headache, nausea, and fatigue were among the more common adverse drug reactions in omaveloxolone-treated patients. In a post hoc propensity-matched analysis, omaveloxolone-treated patients in the OLE progressed by 3 points at Year 3 versus 6.6 points in an untreated matched cohort. Conclusions: Patients who received omaveloxolone showed a significantly stabilized neurological function and slowing of FA progression, as measured by mFARS.

Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.

Background: In intracerebral hemorrhage (ICH), hematoma expansion (HE) is a major predictor of mortality and morbidity. A rapid approach, including oral anticoagulant (OAC) reversal and blood pressure (BP) reduction, both <60 min from arrival, improves outcomes. We aimed to evaluate current time metrics in the management of anticoagulant-associated intracerebral hemorrhage (AAICH) and their impact on HE in a high-income setting. Methods: Consecutive AAICH patients presenting to a high-volume stroke center (2017-2023) were retrospectively identified. Clinical and imaging data were merged, with baseline and follow-up hematoma volumes quantified using 3D Slicer segmentation software. Results: Of 75 AAICH patients, 62 received antihypertensives and 52 OAC reversal, with median(IQR) times to BP control: 87.5 (61-207) minutes and median time to OAC reversal: 67.5 (49-96) minutes. Only 14 (23%) and 23 (44%) achieved treatment targets <60 minutes, respectively, and 7 (9%) patients achieving both targets. HE occurred in 27 of 48 patients with follow-up imaging. Median time to target BP was significantly longer in those with HE (186.5 (87-317) min) compared to those without HE (70 (56-104) min), p=0.01. Conclusions: Current management of AAICH remains heterogeneous, with considerable treatment delays regarding BP control and OAC reversal. These findings support the implementation of standardized protocols to optimize AAICH treatment.

Background: Location-specific hematoma volume thresholds are associated with poor outcomes and can inform surgical trial inclusion criteria and clinical decision rules for hematoma evacuation. Methods: We performed a secondary analysis of the ATACH-2 and INTERACT2 clinical trials. We evaluated the associations between intraparenchymal location-specific hematoma volume cutoffs (basal ganglia, thalamus and lobar) and poor outcome (modified Rankin Scale 4-6). Using 24-hour CT scans, we calculated Youden’s index for each hematoma location to determine the optimal location-specific volume thresholds that predict outcomes. We calculated odds ratios (OR) of poor outcome through multivariable logistic regression models for each location. Results: Out of 1691 patients, 919, 551 and 221 were diagnosed with basal ganglia, thalamus and lobar intracerebral hemorrhage (ICH), respectively. Location-specific hematoma volume cutoffs most predictive of a poor outcome (mRS 4-6) were 22.24 mL for basal ganglia ICH (OR 4.82, 95% CI 3.19-7.27), 8.13 mL for thalamus ICH (OR 2.73, 95% CI 1.62-4.59) and 21.99 mL for lobar ICH (OR 6.31, 95% CI 2.53-15.74). Conclusions: Hematoma volumes associated with poor outcomes vary by location, supporting the idea that location-specific “hematoma volume tolerances” exist. Our results provide important data on location-specific hematoma volume tolerances to inform clinical trials in ICH management.

Background: CIDP is a rare immune-mediated demyelinating neuropathy which has significant phenotypic variability. Despite extensive efforts, a unifying immunopathologicalmechanism remains elusive and this is likely due to etiological heterogeneity among the variant presentations. This is best exemplified by the identification of nodal/paranodal antibodies, such as neurofascin 155 (NF155) in a small subgroup of CIDP patients, who present with a distinct phenotype and embody a poor response to IVIG. Methods: We present the case of a 39-year-old male who presented with a 2-year history of progressive stocking-glove sensory loss and sensory ataxia. Electrodiagnostics confirmed an acquired demyelinating neuropathy, with serum anti-NF155 IgG4. His case was refractory to standard immunomodulatory therapy, including adequate trials of IVIG, steroids, azathioprine, and rituximab. He also had a non-therapeutic trial of PLEX, methotrexate, and tacrolimus. Results: After cessation of all immunomodulatory therapy for 2 years, he had spontaneous remission of his CIDP and near-complete resolution of electrodiagnostic/clinicalabnormalities. Conclusions: This case highlights a unique supra-refractory seropositive CIDP variant which underwent spontaneous remission with near-complete resolution. Delayed effect from rituximab was posited as a contributor, however, the patient had no clinical or electrophysiological improvement 20-months after initiation of anti-CD20 therapy. Current data suggests that CIDP respond to rituximab within 6-12 months.

Background: Cerebral palsy (CP) is a neuromotor disorder whereby gait abnormalities are predominant. Motion analysis is instrumental in management. While 3D kinematic labs exist, they are costly to operate, and the expertise required to interpret limits their availability to only a handful of facilities. In response, we have developed an Automated Intelligence (AI) driven pipeline to automate gait evaluation using 2-dimensional video. We assess the performance of this tool in comparison to traditional evaluation using visual assessment by trained human expert. Methods: A dataset of 109 patients with CP (6–37 years) (GMFCS I – II) was processed using our tool. The Edinburgh Visual Gait Score (EVGS) was derived using videos capturing sagittal and coronal views. Algorithm performance was determined by comparing automated EVGS scores against clinical expert scoring. Results: The AI pipeline successfully analysed 105/109 patient videos. For most EVGS parameters (14/17), the algorithm demonstrated moderate to high accuracy (70-94%), while 3 parameters (hindfoot valgus/varus, maximum lateral trunk shift, pelvic rotation at midstance) demonstrated lower accuracy (58-62%). Conclusions: This study validates the feasibility of an AI-augmented pipeline for automating EVGS-based gait assessments. With ongoing development, this technology has potential to improve accessibility to gait analysis and allows deployment outside of traditional settlings.

Background: Anterior (ACS) and posterior circulation (PCS) stroke patients have different clinical presentations and prognoses, though both benefit from endovascular thrombectomy (EVT). We sought to determine whether ACS and PCS patients treated with EVT differed with regards to treatment metrics and functional outcomes. Methods: We retrospectively analysed theCanadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022. We performed a descriptive analysis of patients divided in two groups (ACS= carotid artery and its branches, PCS= vertebrobasilar system). Results: Of the 6391 patients included (5929 ACS and 462 PCS), PSC patients were younger (67 vs. 71.3, p<0.001), more often male (61.9% vs. 48.6%, p<0.001), had longer (in minutes) onset-to-door (362 vs. 256, p<0.001), door-to-needle (172 vs. 144, p=0.0016), and onset-to-puncture (459 vs. 329, p<0.001) times. They were less often thrombolyzed (39.8% vs. 50.4%, p<0.001), and more frequently underwent general anesthesia (47.6% vs. 10.6%, p<0.001). Successful reperfusion and functional independence at 90 days were similar between the two groups. Conclusions: Patients with PCS had worst treatment metrics than ACS. Strategies to improve PCS management times are critical to decrease these disparities, including faster pre-hospital recognition and in-hospital workflows.

Background: Due to the peculiar location of central neurocytoma, gross total resection is often challenging, and adjuvant radiotherapy is sometimes indicated. Factors associated with outcome are not well addressed in the literature Methods: A multicenter retrospective cohort study among 11 centers in Saudi Arabia including histologically confirmed central neurocytoma between 2000-2022. Results: A total of 104 patients were included. Pre-operative mRS was 0-2 in 93% of the cases. Gross total resection (GTR) was achieved in 50.7%. Radiotherapy was needed in 40% and Ventriculoperitoneal shunt in 38.6%. Favorable outcome was observed in 81.7%. Factors associated with worse outcome included initial mRs of ≥3, tumor size ≥50 mm, and atypical/anaplastic histology. Disease progression was observed in 18 (17.8%). Five-year absolute survival rate was 91.55%. The only significant predictor of disease progression was the presence of atypical features or anaplasia (P .007). Extent of surgical resection (P 0.877) wasn’t associated with disease progression. Post operative radiotherapy didn’t alter residual progression in patients with subtotal resection (P .170) nor the recurrence rate in those with GTR (.365) Conclusions: Central Neurocytoma cases have a high survival rate with a favourable mRs score at long-term follow up. The extent of resection didn’t alter disease progression nor did the adjuvant radiotherapy

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.

Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.

Background: Eccrine carcinoma is a rare skin tumor arising in eccrine sweat glands with a predilection for older adults. Over 30% of cases occur in the head and neck. Local and distal metastases are common. Prognosis is poor with regional recurrence in up to 19% of cases. Imaging is indicated in high-risk disease. Methods: We present a case report of eccrine carcinoma in the scalp with perineural metastasis to the left trigeminal nerve. Results: A seventy-nine-year-old male with a history of left temporal scalp pre-cancerous lesion treated with liquid nitrogen two years prior presented with left facial pain and paresthesia. The gadolinium-enhanced MRI head showed a tiny sub-centimetre spiculated subcutaneous lesion in the left temporal scalp and perineural enhancement along the left auricotemporal, V3 and trigeminal nerves. Subsequent excisional biopsy of the temporal lesion showed a poorly differentiated eccrine carcinoma without local perineural invasion. Conclusions: Undifferentiated facial pain is a frequent indication for head imaging, usually with low diagnostic utility. However, scrutiny for perineural enhancement is necessary to avoid missing a potentially deadly process. Eccrine carcinoma is a rare type of skin cancer. Small, painless, indolent primary lesions may be overlooked clinically. Radiologists can affect outcomes in these cases.

Background: COMISA (comorbid insomnia and obstructive sleep apnea) is associated with daytime functioning and cognitive impairments. This post hoc analysis assessed the impact of lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat insomnia in adults, on morning sleepiness/alertness in participants with COMISA. Methods: Of the overall population (n=1006), 410 (40.8%) adults (≥55 years) with comorbid insomnia disorder and mild obstructive sleep apnea (apnea-hypopnea-index, 5–≤15 events/h) from Study E2006-G000-304 (NCT02783729), a 1-month, randomized, placebo- and active-controlled study, were analyzed. Participants received placebo (PBO), LEM 5mg (LEM5), LEM 10mg (LEM10), or zolpidem tartrate 6.25mg (not reported). A daily sleep diary assessed morning sleepiness/alertness (1, extremely sleepy to 9, extremely alert). Participants (%) shifting from baseline mild/moderate sleepiness (≤3) towards greater alertness (4, 5, or >5) during the first/last 7 mornings of the study were analyzed. Results: At baseline, 17/75 (22.7%), 36/112 (32.1%), and 28/104 (26.9%) participants with COMISA receiving PBO, LEM5, or LEM10, respectively, reported mild/moderate sleepiness. Across the first/last 7 mornings, more participants shifted from mild/moderate sleepiness towards alertness with LEM5 (66.7%, 82.9%) and LEM10 (64.3%, 75.0%) versus PBO (47.1%, 64.7%), respectively. Conclusions: A greater percentage of participants with COMISA experienced improvements in morning sleepiness across the treatment period with LEM versus PBO.